Chromosomal hyperdiploidy is the defining genetic signature in 40-50% of myeloma (MM) patients. We characterize hyperdiploid-MM (H-MM) in terms of its clinical and prognostic features in a cohort of ...220 H-MM patients entered into clinical trials. Hyperdiploid-myeloma is associated with male sex, kappa immunoglobulin subtype, symptomatic bone disease and better survival compared to nonhyperdiploid-MM (median overall survival 48 vs 35 months, log-rank P = 0.023), despite similar response to treatment. Among 108 H-MM cases with FISH studies for common genetic abnormalities, survival is negatively affected by the existence of immunoglobulin heavy chain (IgH) translocations, especially those involving unknown partners, while the presence of chromosome 13 deletion by FISH did not significantly affect survival (median overall survival 50 vs 47 months, log-rank P = 0.47). Hyperdiploid-myeloma is therefore a unique genetic subtype of MM associated with improved outcome with distinct clinical features. The existence of IgH translocations but not chromosome 13 deletion by FISH negatively impacts survival and may allow further risk stratification of this population of MM patients.
Background
Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic ...combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry.
Methods
Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression.
Result
A total of 1002 patients were included (doublets,
n
= 653; anthracycline-based triplets,
n
= 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78–1.05),
p
=
0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7–12.3) vs. 9.9 (95% CI, 9.2–11.4) months, HR 0.91 (CI 95%, 0.76–1.083), and (log-rank test,
p
=
0.226). Response rates (42.1 vs. 33.1%,
p
=
0.12) and PFS (HR 0.95, CI 95%, 0.80–1.13, log-rank test,
p
=
0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3–4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision.
Conclusion
Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant of concern has spread rapidly across Brazil since late 2020, causing substantial infection and death waves. Here we used ...individual-level patient records after hospitalization with suspected or confirmed coronavirus disease 2019 (COVID-19) between 20 January 2020 and 26 July 2021 to document temporary, sweeping shocks in hospital fatality rates that followed the spread of Gamma across 14 state capitals, during which typically more than half of hospitalized patients aged 70 years and older died. We show that such extensive shocks in COVID-19 in-hospital fatality rates also existed before the detection of Gamma. Using a Bayesian fatality rate model, we found that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates were primarily associated with geographic inequities and shortages in healthcare capacity. We estimate that approximately half of the COVID-19 deaths in hospitals in the 14 cities could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization and pandemic preparedness are critical to minimize population-wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries.
This study focused on factors associated with antiretroviral therapy (ART) adherence and quality of life among transgenderwomen in Sao Paulo, Brazil, using univariable and adjusted analysis. ...Adherence was evaluated with a self-report tool and with HIV viral load (VL) measurement. PROQOL-HIV was used to assess quality of life. 106 TGW with median 41 years old were included; most were white (56%) and had >10 years of education (57%). Median time since HIV/AIDS diagnosis was 10 years. Overall, participants had high T CD4+ counts (median 659 cells/mm
3
) and most (75%) had undetectable HIV VL. 85% were considered adherent using self-report (95%CI 77-91), whereas 72% (95%CI 62-80) were considered adherent when self-report and undetectable HIV VL were analyzed jointly. Older age was associated with higher ART adherence; each year increase in age was associated with 5% higher odds of adherence (p = 0.021). Quality of life ranged from good-excellent in 5 of 8 domains. Younger age, lower education, higher time since HIV diagnosis, comorbidities, illicit drugs use and depression were associated with lower PROQOL scores in specific domains in univariable analysis, while depression was also associated with lower total PROQOL score even after adjustment for age, comorbidities and time since HIV diagnosis (p = 0.048).
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Abstract
Introduction
Progression of hypertrophic cardiomyopathy (HCM) with incident left ventricular (LV) dysfunction (HCM-LVSD) is associated with poor prognosis and advanced heart failure (HF). ...Prevalence ranges from 5–10% in previous studies. Identification of predictors of adverse remodeling may improve risk stratification and prognostication in HCM.
Purpose
To identify predictors of HCM-LVSD in a nationwide cohort of HCM patients (pts).
Methods
Retrospective study including all HCM pts enrolled in a European country-based nationwide registry. HCM-LVSD group included pts with LV ejection fraction (LVEF) ≤50% at baseline and pts who developed LV dysfunction/dilated phenotype during follow-up. Multivariate logistic regression was performed to identify predictors of HCM-LVSD.
Results
1042 HCM patients (57.8% male, mean age at diagnosis 52 years) were included, of whom 81 (8%) belonged to the HCM-LVSD group. HCM-LVSD pts were mostly male (60.5%) and tended to be older at the time of diagnosis than those without LVSD (55 vs 52 years, p=0.054). HCM-LVSD pts were more often symptomatic at the index visit (84.1% vs 65.2%, p<0.001), with more functional impairment (New York Heart Association class III–IV: 18.5% vs 9.2%, p=0.021). Atrial fibrillation (21.3% vs 8.6%, p<0.001) and intraventricular conduction disturbances (28.6% vs 14.4%, p=0.002) were more prevalent in HCM-LVSD pts. HCM-LVSD pts had higher baseline left atrium (LA) volumes (52 vs 39 ml, p=0.001), lower LVEF (50 vs 67%, p<0.001) and higher rates of mitral regurgitation (79.0% vs 65.1%, p=0.011). Prevalence of obstructive HCM was lower in the HCM-LSVD group (25.3% vs 40.9%, p=0.007). Presence of late gadolinium enhancement (92.6% vs 74.6%, p=0.035) was more common in pts with LVSD. Baseline N-terminal pro–B-type natriuretic peptide was higher in HCM-LVSD (3839 vs 1281 pg/ml, p=0.027). There were no differences in the number and type of genetic variants between groups. In HCM-LVSD pts, implantation of cardioverter-defibrillators for secondary prevention was more frequent (28.6% vs 6.4%, p=0.002), as was the use of pacemaker (16.7% vs 7.0%, p=0.002). During a mean follow-up of 5.3±6.1 years, hospitalization for HF (50.0% vs 11.3%) and all-cause mortality (12.3% vs 2.9%, p<0.001) were more frequent in HCM-LVSD group.
After multivariate analysis, higher LA volume (odds ratio OR 1.03, 95% confidence interval CI 1.01–1.05, p=0.003) and nonobstructive HCM (OR 2.74, 95% CI 1.03–7.27, p=0.043) were independent predictors of HCM-LVSD.
Conclusions
In this large nationwide cohort of HCM pts, prevalence of LVSD was 8%, in line with existing literature. In this cohort, larger LA volumes and nonobstructive HCM predicted progression to HCM-LVSD.
Funding Acknowledgement
Type of funding sources: None.
Abstract
Introduction
The EXPLORER-HCM trial evaluated the safety and efficacy of Mavacamten, a cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy (HCM). Mavacamten ...improved symptoms, exercise capacity and left ventricular outflow tract (LVOT) obstruction. However, the proportion of patients eligible for this therapy in real practice remains unclear.
Purpose
To determine the prevalence of eligibility criteria for Mavacamten and to describe the profile of patients complying with EXPLORER-HCM criteria in a nationwide cohort.
Methods
Cross-sectional study including all HCM patients enrolled in a European country-based nationwide registry. Presence of EXPLORER-HCM inclusion ≥18 years, obstructive HCM (LVOT gradient ≥50 mmHg), left ventricular ejection fraction (LVEF) ≥55%, New York Heart Association (NYHA) class II–III and exclusion criteria syncope or sustained ventricular tachycardia with exercise were analyzed.
Results
Of 1042 patients included in this analysis (57.8% male, mean age at diagnosis 52 years, 39.6% obstructive HCM), 45 met the EXPLORER-HCM inclusion criteria and, after applying exclusion criteria, 30 patients were eligible for therapy with Mavacamten.
Eligible patients were all Caucasian, mostly female (63.3%), with a mean age at diagnosis of 58±14 years. All patients presented with heart failure symptoms, and were mostly in NYHA class II (83.3%); 4 patients (13.3%) presented with atrial fibrillation. In the baseline echocardiogram, mean LVEF was 68±9%; mean interventricular septum thickness was 20±4 mm; most patients presented with systolic anterior motion of the mitral valve (96.7%) and mitral regurgitation (96.7%). In cardiac magnetic resonance imaging evaluation, maximal wall thickness was 22±4 mm and 76.9% had late gadolinium enhancement. A pathogenic or likely pathogenic HCM gene variant was identified in 5 patients (MYH7 and MYBPC3 gene mutations).
In this group, 86.2% of patients were treated with beta-blockers and 34.5% with calcium channel antagonists. Only 1 patient was on Disopyramide. Septal reduction techniques were used in 43.3% of patients: alcohol septal ablation and septal myectomy were performed in 7 (23.3%) and 6 (20.0%) patients, respectively. Cardioverter-defibrillators were implanted in 2 patients for primary prevention of sudden cardiac death, and 6 patients received a pacemaker for bradycardia indications.
Conclusion
Specific therapies remain an unmet need in HCM. In this large nationwide cohort, only 2.9% of patients were eligible for therapy with Mavacamten according to EXPLORER-HCM criteria. Among patients complying with the study criteria, invasive septal reduction therapies were offered to a high proportion of patients. Further real-world data are warranted to estimate the proportion of HCM patients that will benefit from Mavacamten.
Funding Acknowledgement
Type of funding sources: None.
An outbreak of a disease characterized by emaciation, dermatitis with erythema, alopecia, foul-smelling exudation, crusting, hyperpigmentation, lichenification, and edema of fore- and hindlimbs, ...chest and dewlap is described affecting cattle in the State of Alagoas, Northeastern Brazil. Microscopically, the main lesions were characterized by diffuse dermatitis with infiltration of lymphocytes, histiocytes, parakeratotic hyperkeratosis and acanthosis. The plant Tephrosia noctiflora, which exhibited signs of consumption, infested the grazing areas of cattle. To test its toxicity, T. noctiflora was harvested, dried in the shade, crushed and sourced at a concentration of 50% mixed with commercial food for three guinea pigs. The main clinical signs in guinea pigs included weight loss and multifocal, moderate to severe areas of alopecia, diffuse erythema of the skin, vaginal edema and hematuria. Microscopically, lymphocytic and histiocytic dermatitis, parakeratotic hyperkeratosis and acanthosis were noted in guinea pigs. This experiment confirms that T. noctiflora is the cause of outbreaks of dermatitis observed in cattle grazing in areas infested by this plant.
Display omitted
•Tephrosia noctiflora intoxication causes severe dermatitis and emaciation in cattle.•Alopecia, crusting, hyperpigmentation, and lichenification are observed in the skin.•Edema of fore- and hindlimbs, chest and dewlap are also observed in severely intoxicated cattle.•Intoxications causes economic losses due to death of animals, poor weight gain, and low quality of the carcasses.•Guinea pigs are sensitive to the intoxication caused by T. noctiflora.
Sea turtles are an iconic group of marine megafauna that have been exposed to multiple anthropogenic threats across their different life stages, especially in the past decades. This has resulted in ...population declines, and consequently many sea turtle populations are now classified as threatened or endangered globally. Although some populations of sea turtles worldwide are showing early signs of recovery, many still face fundamental threats. This is problematic since sea turtles have important ecological roles. To encourage informed conservation planning and direct future research, we surveyed experts to identify the key contemporary threats (climate change, direct take, fisheries, pollution, disease, predation, and coastal and marine development) faced by sea turtles. Using the survey results and current literature, we also outline knowledge gaps in our understanding of the impact of these threats and how targeted future research, often involving emerging technologies, could close those gaps.
Electron and photon triggers covering transverse energies from 5
GeV
to several
TeV
are essential for the ATLAS experiment to record signals for a wide variety of physics: from Standard Model ...processes to searches for new phenomena in both proton–proton and heavy-ion collisions. To cope with a fourfold increase of peak LHC luminosity from 2015 to 2018 (Run 2), to
2.1
×
10
34
cm
-
2
s
-
1
, and a similar increase in the number of interactions per beam-crossing to about 60, trigger algorithms and selections were optimised to control the rates while retaining a high efficiency for physics analyses. For proton–proton collisions, the single-electron trigger efficiency relative to a single-electron offline selection is at least 75% for an offline electron of 31
GeV
, and rises to 96% at 60
GeV
; the trigger efficiency of a 25
GeV
leg of the primary diphoton trigger relative to a tight offline photon selection is more than 96% for an offline photon of 30
GeV
. For heavy-ion collisions, the primary electron and photon trigger efficiencies relative to the corresponding standard offline selections are at least 84% and 95%, respectively, at 5
GeV
above the corresponding trigger threshold.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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